Combined mutations in pre-s/surface and core promoter/precore regions of hepatitis B virus increase the risk of hepatocellular carcinoma: a case-control study.
BACKGROUND
We sought to investigate the role of sequence variations in pre-S/surface and basal core promoter (BCP)/precore regions of the hepatitis B virus (HBV) in hepatocellular carcinoma (HCC).


METHODS
The direct sequencing in pre-S/surface and BCP/precore regions of HBV was determined for 80 patients with HCC and 160 control patients with HBV infection.


RESULTS
Compared with control patients, patients with HCC had higher frequencies of pre-S deletions and amino acid substitutions at codon 4, 7, and 81 in pre-S1 genes; at the start codon in pre-S2 genes; and at codon 68 in surface genes. Patients also had a lower frequency of amino acid substitution at codon 2 in pre-S2 genes, compared with control patients. In BCP/precore regions, patients with HCC had higher frequencies of C or G1753, A1762/T1764, T1846, and A1899. Multivariate analysis showed that pre-S deletions, I68T surface gene, T1762/A1764, and A1899 were independent factors associated with the development of HCC. The HBV strain with a complex mutation pattern rather than a single mutation was associated with HCC, and the HCC risks increased for patients having these factors in combination.


CONCLUSIONS
Pre-S deletions, I68T in surface gene, T1762/A1764, and A1899 were independent risk factors for HCC. Combination of these viral mutations appeared to increase the risk of HCC.
Chen
Chien-Hung
CH
Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, Taiwan.
Changchien
Chi-Sin
CS
Lee
Chuan-Mo
CM
Hung
Chao-Hung
CH
Hu
Tsung-Hui
TH
Wang
Jing-Houng
JH
Wang
Jyh-Chwan
JC
Lu
Sheng-Nan
SN
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006509:Hepatitis B / Q000150:complications* / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors
D006514:Hepatitis B Surface Antigens